Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2023 Jan;25(1):198-207. doi: 10.1111/dom.14864. Epub 2022 Sep 27.
To study the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved.
A total of 24 people with type 2 diabetes (T2D) (age: 66 ± 6 years; body mass index: 31.0 ± 3 kg/m ; estimated glomerular filtration rate: 90 ml/min/1.73m ) received a 1-week treatment with empagliflozin 10 mg once daily, losartan 50 mg once daily, their combination, and placebo, in a randomized double-blind crossover design, with 4-week washout periods in between. Blood pressure, arterial stiffness, autonomic nervous system activity and plasma volume, extracellular fluid and serum albumin were assessed.
Versus placebo (139 mmHg), empagliflozin reduced systolic blood pressure (SBP) by 8 mmHg (P = .001), losartan by 12 mmHg (P = .001) and empagliflozin + losartan by 15 mmHg (P < .001). Combination therapy had a larger SBP-lowering effect versus empagliflozin monotherapy (-7 [95% CI -12; -2] mmHg) and numerically larger effects versus losartan monotherapy (-3 [-8; 2] mmHg). Empagliflozin reduced sympathetic nervous system (SNS) activity, arterial stiffness and extracellular fluid, while increasing serum albumin. Losartan reduced SNS activity and arterial stiffness. Combination therapy induced volume contraction variables, together with a reduction in SNS activity and arterial stiffness.
In people with T2D, SGLT2 inhibition in combination with an ARB had a larger blood pressure-lowering effect versus placebo than either of the drugs alone. Our data further suggest that the mechanisms underlying these blood pressure reductions at least partially differ between these agents.
研究钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂恩格列净、血管紧张素受体阻滞剂（ARB）氯沙坦及其联合应用对血压的影响，并探讨可能涉及的机制。
共纳入 24 例 2 型糖尿病（T2D）患者（年龄：66±6 岁；体重指数：31.0±3kg/m2；估算肾小球滤过率：90ml/min/1.73m2），采用随机、双盲、交叉设计，在 1 周内分别接受恩格列净 10mg 每日 1 次、氯沙坦 50mg 每日 1 次、二者联合应用和安慰剂治疗，每个治疗周期之间有 4 周洗脱期。评估血压、动脉僵硬度、自主神经系统活动和血浆容量、细胞外液和血清白蛋白。
与安慰剂（139mmHg）相比，恩格列净降低收缩压（SBP）8mmHg（P=0.001），氯沙坦降低 12mmHg（P=0.001），恩格列净联合氯沙坦降低 15mmHg（P<0.001）。与恩格列净单药治疗相比（-7[95%CI-12；-2]mmHg），联合治疗的 SBP 降低效果更大，与氯沙坦单药治疗相比（-3[-8；2]mmHg），联合治疗的效果也更大。恩格列净降低交感神经系统（SNS）活性、动脉僵硬度和细胞外液，增加血清白蛋白。氯沙坦降低 SNS 活性和动脉僵硬度。联合治疗诱导容量收缩变量，同时降低 SNS 活性和动脉僵硬度。
在 T2D 患者中，与安慰剂相比，SGLT2 抑制剂联合 ARB 治疗的降压效果优于两种药物单独治疗。我们的数据进一步表明，这些药物降压作用的机制至少部分不同。
